Genetic Profile Identified for Dementia with Lewy Bodies

Dementia with Lewy bodies has a unique genetic profile, distinct from those of Alzheimer's disease or Parkinson's disease, according to the first large-scale genetic study of this common type of dementia.

Dementia with Lewy bodies (DLB) is the second most common form of dementia in elderly people but has been overshadowed in the medical field, partly because of similarities between dementia with Lewy bodies, Parkinson's disease, and Alzheimer's disease.

An international team of 65 scientists from 11 countries collaborated with those at University College London (London, UK) collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected after participant examination. The team genotyped 1,743 patients with dementia with Lewy bodies (DLB), including both clinical samples and 1,324 pathological samples assessed post-mortem, and 4,454 controls.

The investigators found that two of the genetic loci that were found to be significantly associated with DLB, Apolipoprotein E (APOE) and glucocerebrosidase (GBA), bore the same associations to DLB as they do to Alzheimer's and Parkinson's, respectively. Another one of the loci identified alpha-synuclein (SNCA), is also associated with Parkinson's, but differently as the team found that a different part of the gene is linked to DLB. They also found preliminary evidence for a gene locus that had not been previously associated with DLB, but the results did not reach significance. The team also found that a few loci that are associated with Alzheimer's and Parkinson's do not appear to be associated with DLB. They were able to identify a heritability estimate of DLB for the first time, at 36%, which is similar to that of Parkinson's. The heritability was particularly high for four specific chromosomes, suggesting that further studies could focus on those chromosomes to identify novel loci.

Rita Guerreiroa, PhD, a senior lecturer and the lead author of the study said, “As the gene loci that had previously been associated with DLB were also implicated in Alzheimer's and Parkinson's, it was unclear if DLB's genetic roots were simply a combination of the other two diseases. We've confirmed that instead, it has its own unique genetic profile.” The study was published in the January 2018 edition of journal The Lancet Neurology.

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